This project is designed to (a) identify human genes which are important in the control of gene expression and to (b) determine gene linkage relationships of these and other gene markers. These aspects of human development will be studied in a parasexual genetic way employing man-mouse somatic cell hybrids. Many of these studies involve the genetic characterization of a group of acid hydrolases associated with lysosomes. Genes important in the final expression of lysosomal hydrolases will be studied employing normal and enzyme deficient human fibroblasts in hybrid combinations with mouse cells. Several of the enzymes are associated with such neurodegenerative diseases as Tay Sachs disease, Sandhoff-Jatzkewitz disease, metachromatic leukodystrophy and generalized gangliosidosis. These studies are designed to provide a better understanding of the genetics of lysosomal enzymes and their deficiencies and, hopefully, to aid in the prenatal diagnosis of lysosomal storage diseases. It is hoped that such information will help to construct models of lysosomal biogenesis and regulation. Proliferating man-mouse somatic cell hybrids is particulary suited for this study since human chromosomes but not mouse chromosomes are lost which provides the mechanism for dissecting the genetic components necessary for the final expression of a lysosomal enzyme. BIBLIOGRAPHIC REFERENCES: Shows, T. B. 1975. Genetics, expression, and characterization of isozymes in somatic cell hybrids. Isozymes, III. Developmental Biology, p. 619 (Academic Press). Shows, T. B. 1975. Gene markers for mapping the human genome: The 1974 listing. Cytogenet. and Cell Genet. 14:29-37.